Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality

Kaori Sasai, J. M. Parant, M. E. Brandt, J. Carter, H. P. Adams, S. A. Stass, A. M. Killary, Hiroshi Katayama, S. Sen

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Aurora A (also known as STK15/BTAK in humans), a putative oncoprotein naturally overexpressed in many human cancers, is a member of the conserved Aurora protein serine/threonine kinase family that is implicated in the regulation of G2-M phases of the cell cycle. In vitro studies utilizing antibody microinjection, siRNA silencing and small molecule inhibitors have indicated that Aurora A functions in early as well as late stages of mitosis. However, due to limitations in specificity of the techniques, exact functional roles of the kinase remain to be clearly elucidated. In order to identify the physiological functions in vivo, we have generated Aurora A null mouse embryos, which show severe defects at 3.5 d.p.c. (days post-coitus) morula/blastocyst stage and lethality before 8.5 d.p.c. Null embryos at 3.5 d.p.c. reveal growth retardation with cells in mitotic disarray manifesting disorganized spindle, misaligned and lagging chromosomes as well as micronucleated cells. These findings provide the first unequivocal genetic evidence for an essential physiological role of Aurora A in normal mitotic spindle assembly, chromosome alignment segregation and maintenance of viability in mammalian embryos.

Original languageEnglish
Pages (from-to)4122-4127
Number of pages6
JournalOncogene
Volume27
Issue number29
DOIs
Publication statusPublished - Jul 3 2008
Externally publishedYes

Fingerprint

Spindle Apparatus
Coitus
Chromosomes
Embryonic Structures
Aurora Kinases
Mammalian Embryo
Morula
Chromosome Segregation
G2 Phase
Protein-Serine-Threonine Kinases
Oncogene Proteins
Microinjections
Blastocyst
Mitosis
Cell Division
Small Interfering RNA
Cell Cycle
Phosphotransferases
Maintenance
Antibodies

Keywords

  • Chromosome segregation
  • Cre-LoxP recombination
  • Mitotic spindle
  • Morula/blastocyst
  • Mouse Aurora kinase A (Aurka) gene

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality. / Sasai, Kaori; Parant, J. M.; Brandt, M. E.; Carter, J.; Adams, H. P.; Stass, S. A.; Killary, A. M.; Katayama, Hiroshi; Sen, S.

In: Oncogene, Vol. 27, No. 29, 03.07.2008, p. 4122-4127.

Research output: Contribution to journalArticle

Sasai, K, Parant, JM, Brandt, ME, Carter, J, Adams, HP, Stass, SA, Killary, AM, Katayama, H & Sen, S 2008, 'Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality', Oncogene, vol. 27, no. 29, pp. 4122-4127. https://doi.org/10.1038/onc.2008.47
Sasai, Kaori ; Parant, J. M. ; Brandt, M. E. ; Carter, J. ; Adams, H. P. ; Stass, S. A. ; Killary, A. M. ; Katayama, Hiroshi ; Sen, S. / Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality. In: Oncogene. 2008 ; Vol. 27, No. 29. pp. 4122-4127.
@article{36268103b23c4884838d2803ae2e0434,
title = "Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality",
abstract = "Aurora A (also known as STK15/BTAK in humans), a putative oncoprotein naturally overexpressed in many human cancers, is a member of the conserved Aurora protein serine/threonine kinase family that is implicated in the regulation of G2-M phases of the cell cycle. In vitro studies utilizing antibody microinjection, siRNA silencing and small molecule inhibitors have indicated that Aurora A functions in early as well as late stages of mitosis. However, due to limitations in specificity of the techniques, exact functional roles of the kinase remain to be clearly elucidated. In order to identify the physiological functions in vivo, we have generated Aurora A null mouse embryos, which show severe defects at 3.5 d.p.c. (days post-coitus) morula/blastocyst stage and lethality before 8.5 d.p.c. Null embryos at 3.5 d.p.c. reveal growth retardation with cells in mitotic disarray manifesting disorganized spindle, misaligned and lagging chromosomes as well as micronucleated cells. These findings provide the first unequivocal genetic evidence for an essential physiological role of Aurora A in normal mitotic spindle assembly, chromosome alignment segregation and maintenance of viability in mammalian embryos.",
keywords = "Chromosome segregation, Cre-LoxP recombination, Mitotic spindle, Morula/blastocyst, Mouse Aurora kinase A (Aurka) gene",
author = "Kaori Sasai and Parant, {J. M.} and Brandt, {M. E.} and J. Carter and Adams, {H. P.} and Stass, {S. A.} and Killary, {A. M.} and Hiroshi Katayama and S. Sen",
year = "2008",
month = "7",
day = "3",
doi = "10.1038/onc.2008.47",
language = "English",
volume = "27",
pages = "4122--4127",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "29",

}

TY - JOUR

T1 - Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality

AU - Sasai, Kaori

AU - Parant, J. M.

AU - Brandt, M. E.

AU - Carter, J.

AU - Adams, H. P.

AU - Stass, S. A.

AU - Killary, A. M.

AU - Katayama, Hiroshi

AU - Sen, S.

PY - 2008/7/3

Y1 - 2008/7/3

N2 - Aurora A (also known as STK15/BTAK in humans), a putative oncoprotein naturally overexpressed in many human cancers, is a member of the conserved Aurora protein serine/threonine kinase family that is implicated in the regulation of G2-M phases of the cell cycle. In vitro studies utilizing antibody microinjection, siRNA silencing and small molecule inhibitors have indicated that Aurora A functions in early as well as late stages of mitosis. However, due to limitations in specificity of the techniques, exact functional roles of the kinase remain to be clearly elucidated. In order to identify the physiological functions in vivo, we have generated Aurora A null mouse embryos, which show severe defects at 3.5 d.p.c. (days post-coitus) morula/blastocyst stage and lethality before 8.5 d.p.c. Null embryos at 3.5 d.p.c. reveal growth retardation with cells in mitotic disarray manifesting disorganized spindle, misaligned and lagging chromosomes as well as micronucleated cells. These findings provide the first unequivocal genetic evidence for an essential physiological role of Aurora A in normal mitotic spindle assembly, chromosome alignment segregation and maintenance of viability in mammalian embryos.

AB - Aurora A (also known as STK15/BTAK in humans), a putative oncoprotein naturally overexpressed in many human cancers, is a member of the conserved Aurora protein serine/threonine kinase family that is implicated in the regulation of G2-M phases of the cell cycle. In vitro studies utilizing antibody microinjection, siRNA silencing and small molecule inhibitors have indicated that Aurora A functions in early as well as late stages of mitosis. However, due to limitations in specificity of the techniques, exact functional roles of the kinase remain to be clearly elucidated. In order to identify the physiological functions in vivo, we have generated Aurora A null mouse embryos, which show severe defects at 3.5 d.p.c. (days post-coitus) morula/blastocyst stage and lethality before 8.5 d.p.c. Null embryos at 3.5 d.p.c. reveal growth retardation with cells in mitotic disarray manifesting disorganized spindle, misaligned and lagging chromosomes as well as micronucleated cells. These findings provide the first unequivocal genetic evidence for an essential physiological role of Aurora A in normal mitotic spindle assembly, chromosome alignment segregation and maintenance of viability in mammalian embryos.

KW - Chromosome segregation

KW - Cre-LoxP recombination

KW - Mitotic spindle

KW - Morula/blastocyst

KW - Mouse Aurora kinase A (Aurka) gene

UR - http://www.scopus.com/inward/record.url?scp=46449107956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46449107956&partnerID=8YFLogxK

U2 - 10.1038/onc.2008.47

DO - 10.1038/onc.2008.47

M3 - Article

C2 - 18345035

AN - SCOPUS:46449107956

VL - 27

SP - 4122

EP - 4127

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 29

ER -